Approaches to the Synthesis of Triterpenoids. II. Some Tetracyclic Precursors Suitable for Conversion into Pentacyclic Triterpenoids

Abstract

The stereoselective total synthesis of several partially reduced chrysene derivatives, suitable as precursors for a variety of triterpenoids, is described. The key reaction in the most efficient route involves the highly stereoselective reductive alkylation of a cyclic a$-unsaturated ketone with ally1 bromide in lithium-ammonia, using water as a proton donor.La synthtse totale et stertoselective de plusieurs derivts partiellement reduits du chrysene est dtcrite; ces dtrivts sont utilists en tant que precurseurs d'un certain nombre de composts triterpeniques. La rtaction cruciale, par la methode la plus efficace, implique une alkylation par reduction hautement sttrtoselective d'une cttone a$-insaturte par le bromure d'allyle dans un melange lithium-ammoniaque et en utilisant I'eau comme source de protons.

Approaches to the synthesis of triterpenoids. IV. The ABC + E ring approach to the pentacyclic triterpene skeleton. Synthesis of a pentacyclic compound suitable for triterpene synthesis

“…Acid hydrolysis of the ethylene ketal group provided the crystalline mixture of ketones 4b. T h e stereochemistry of the alkylation step at C(1) is based on the observations of previous workers (5,7,8) a n d o n the use of benzene induced shifts of the methyl signals observed in the nmr spectra of our alkylated co~npounds (5). This assignment is confirmed by the X-ray structure determination quoted later.…”

“…We therefore turned our attention to the cyclisation in the absence of the C(1a)-C(I0) double bond in 4b. We have previously shown (5,12) that hydrogenation of cornpounds re-; lated to 4 proceeds stereoselectively depending on the conditions used. In the event, reduction of mixture 4b by hydrogen in boiling xylene using palladiun1-011-charcoal as the catalyst was readily accon~plished to yield the mixture of diketones 11.…”

Designing Total Syntheses

“…This is one of the general annelation methods developed by Stork and colleagues [11,61]; its major advantage is the ease with which the protective group is removed, though it suffers from relative low reactivity of the bromide group [62]. In the total synthesis of some tetracyclic precursors of pentacyclic triterpenes, ApSimon and colleagues found the tosylate 58 ( X = O ) to be more reactive than the corresponding chloride or bromide [63]. Additional annelating agents include the hemithioketal tosylate 58 (X = S), the dithioketal brosylate 59 [64], and most particularly the isoxazole 60 [65]; improvements in the isoxazole annelation method have been reported [66].…”